Preparation of 6-amino-2,4-bis(dimethylamino)-s-triazine



United States Patent 3,479,353 PREPARATION OF 6-AMINO-2,4-BIS(DIMETHYL- AMINO)-s-TRIAZINE Max L. Petzold and Thomas W. Brooks, Gainesville, Fla.,

and John M. Bane, Jr., Parchment, Mich., assignors, by mesne assignments, to Calgon Corporation, a corporation of Delaware No Drawing. Filed Dec. 26, 1967, Ser. No. 693,142

Int. Cl. C07d 55/24; A01n 9/22 US. Cl. 260-249.6 6 Claims ABSTRACT OF THE DISCLOSURE The title compound, which is known to be useful as a fly sterilant, is made by reacting four moles of dimethylamine with cyanuric chloride in a medium of chloroform, to yield a high-purity reaction product of 2,4-bis (dimethylamino)6-chloro-s-triazine which, Without further purification, is reacted preferably in a dimethyl sulfoxide solution with ammonia. 2O

BACKGROUND OF THE INVENTION The compound 6-amino-2,4-bis(dimethylamino)-s-triazine is known to be useful as a sterilizing agent for house flies. See Example 7 of US. Patent 3,189,521 and compound No. of Table I, p. 458, of Borkovec et al. J. Med. Chem. 10, 457 (May 1967). The compound is also referred to as N ,N ,N ,N -tetramethylmelamine. In the past, the intermediate 2,4-bis(dimethylamino)-6-chloro-striazine has been prepared in the prior art by reacting cyanuric chloride in suspension or in a suitable organic solvent with dimethylamine in a molar ratio of cyanuric chloride/dimethyl amine of about 1:4.2 and, subsequently, purifying the product by distillation or crystallization. 35 Pearlman and Banks teach that all three chlorine atoms of cyarruric chloride are replaced by dimethylamine at 25 C. See W. M. Pearlman and C. K. Banks, J. Am. Chem. Soc. 70, 3726 (1948). The second step of the synthesis is conventionally conducted in pressure equipment with a solvent such as dimethylsulfoxide at operating pressures in the range of to 250 p.s.i.g. See Borkovec et al. I. Medicinal Chem., 10, 457 (1967). See also US. Patents 2,222,350 and 2,228,161.

The processes of the prior art result in substantial quantities of the monoand trisubstituted products. Pearlman and Banks teach that, in reacting cyanuric chloride with dimethyl amine, all three chlorines are replaced at 25 C. See W. M. Pearlman and C. K. Banks, J. Am. Chem. Soc. 70, 3726 (1948). Moreover, in the conversion of 2,4-bis (dimethylamino)-6-chloro-s-triazine to 2-amino-4,6-bis (dimethylamino)-s-triazine, the use of the pressure has been required (see Example II of the present application, and Borkovec et al., I. Medicinal Chem. 10, 457 (1967).

While the prior art has used about 4.2 moles of dimethyl amine to one mole of cyanuric chloride, We are able to use 4.0 moles to achieve an excellent yield of the desired reaction product by performing the reaction in chloroform.

The chemistry of the reaction may be illustrated as follows:

SUMMARY OF THE INVENTION We have found that cyanuric chloride dissolved in chloroform will react with four moles of dimethylamine at temperatures of 5-20 C. to give, 2,4-bis(dimethylamino)-6-ch1oro-s-triazine in good yield and essentially free of the corresponding monosubstituted and trisubstituted products, Z-(dimethylamino)-4,6-dichloro-s-triazine and hexamethylmelamine. After washing the re action mixture free of CH NH.HCl with water, evaporation of the reaction solvent leaves the desired intermediate chloro-s-triazine as a White crystalline material which is sufliciently pure to be used in the subsequent step without having to be distilled or recrystallized.

We also find that the second step, treatment of 2,4-bis (dimethylamino)-6-chloro-s-triazine with ammonia gas to give 2-amino-4,6-bis(dimethylamino)-s-triazine, may be carried out at atmospheric pressure simply by passing ammonia into a dimethylsulfoxide solution of the chloro-striazine at a temperature of to 185 C., preferably -140 C. This procedure circumvents the requirement for high pressure equipment. Instead of dimethyl sulfoxide, We may use any other high boiling (that is, having a boiling point higher than about C.) polar aprotic solvent. Examples of suitable solvents are dimethyl formamide, dimethyl acetamide, N-methyl pyrrolidone, and tetramethyl sulfone. Our preferred temperature for the second reaction is about 130 C.

By virtue of these modifications, the overall process for manufacturing 6-amino-2,4-bis(dimethylamino)-s-triazine is considerably simplified and rendered amenable to commercial scales of operation.

Illustrative of our invention are the following examples:

Example I.Preparation of 2,4-bis(dimethylamino)-6- chloro-s-triazine A IOO-gal. stainless steel jacketed kettle was charged With lbs. of cyanuric chloride and 55 gals. of technical grade chloroform. The kettle was closed and sealed and its contents cooled to 5 C. While holding the temperature of the stirred reaction mixture in the range of 5-20" 0, 140* lbs. of dimethylamine was added as a liquid at a pressure of 23 p.s.i.g. Addition of all of the dimethylamine requires 12-14 hours. The reaction mixture was then washed three times with 25 gal. portions of Water to remove the dimethylamine hydrochloride by-product. The organic phase was then dried over 30 lbs. of anhydrous magnesium sulfate and filtered. The filtrate was returned to the kettle and strip distilled to a pot temperature of 110 C. under a Water aspirator. Upon cooling the residue crystallized and was shown by gas-liquid chromoatogra hic analysis to be better than 95% pure 2,4-bis(dimethylamino)-6-chloro-s-triazine. The yield was lbs. or 94.3% of. theory. The identity of the product Was established from its gas-liquid chromatographic retention time and infrared spectrum by comparison with an authentic sample.

Example II.-Preparation of 2-amino-4,6-bis(dimethylamino)-s-triazine by the high pressure, prior art method A 10 gal. autoclave equipped for agitation by means of 3,479,353 3 4 a dasher and fitted with a rupture disc rated for 600 p.s.i. Crops I and II were combined to give 25.8 lbs. (53.9% at 72 C. was charged with 13.2 lbs. of 2,4-bis(dimethylof theory) of 2-amino-4,6-bis(dimethylamino)-s-triazine. amino)-6-chloro-s-triazine and 5 gal. of dimethylsulfoxide. Our invention may thus be stated to be a process of The autoclave was then sealed and 3.45 lbs. of ammonia making the title compound comprising (1) reacting, in a was added under pressure. The contents were then heated 5 chloroform medium four moles of dimethyl amine with gradually until the internal temperature of the apparatus one mole of cyanuric chloride to obtain about one mole was 130 C. An exotherm was noted during the reaction of 2,4bis(dimethylamino)-6-chloro-s-triazine, and (2) rewhich caused the reaction mixture to reach a temperature acting the reaction product thereof with ammonia gas to of 165 and a pressure of 155 p.s.i.g. After four hours the atmospheric pressure, and a temperature between 70 and exotherm had subsided and the pressure had dropped to 10 185 C. Our invention includes a method of making 6- 45 p.s.i. where it held constant at a temperature of 130 amino-2,4-bis(dimethylamino)-s-triazine by reaction (2). C. The autoclave contents weer then cooled and removed, We claim; the crude product being collected as a solution in dimethyl- Method of making 6 amino z4 bis(dimethylamino) Sulfoxides-triazine comprising (1) reacting, in a chloroform med- Repetitions of this experiment are tabulated below: ium, four moles of dimethyl amine with one mole of Reactor Charge Exp. N0. Triazine Ammonia DMSO Observations 2 13.2 pounds 3.45 pounds." 5 gallons Max. pressure 155 p.s.i.g., max. temp. 165 C' 3 do .do .do Do.

4 "do .do do vliolgnt exotherm, reactor damaged, charge 5 6.6 pounds 1.7 pounds 2.5 gallons... Max. pressure 120 p.s.i.g., max. temp. 138 C.

6 26.4 pounds.-. 6.8 pounds.... 5gallous Exotherm, disc. blew at 440 p.s.i.g. and

185 0., half of charge lost.

The dimethylsulfoxide solutions of crude product from cyanuric chloride to obtain about one mole of 2,4-bis all six runs were combined and poured into gal. of (dimethylamino)-6-chloro-s-triazine, and (2) reacting the water. The solids which precipitated were collected by reaction product thereof inamedium of high boiling polar filtration and air-dried. The crude solid product was then aprotic solvent with ammonia gas at atmospheric presrecrystallized from chloroform (2.2 lbs/l2 l. CHCl sure, and a temperature between 70 and 185 C.

After collecting the first crop of recrystallized product a 2. Method of claim 1 in which the temperature for second crop was collected by evaporating the mother th fi t ti i 5 20 C,

liquors to one-third their volume and collecting by filtra- 3. M th d of l i 1 i hi h th t e atur f th tion. The combined crops amounted to 28.8 lbs. or 48.5% second reaction i 120C140 of theoretical after allowing for materials lost in the blow 4, M thod f l i 1 in hi h th lvent edi The Purified Product melted at and Was for the second reaction is dimethyl sulfoxide.

spectroscopically identical to authentic 2-amino-4,6-bis 5, Method of making 6-amino-2,4-bis(dimethylamino)- (dimethylamino)-s-triazine. 4 s-triazine comprising reacting 2,4-bis(dimethylamino)-6- chloro-s-triazine with ammonia in a medium of dimethylsulfoxide at a temperature between 70 and 185 C. and at atmospheric pressure.

Into a 50-liter Pyrex glass three-neck flask fitted with Method f claim 5 in which the temperature is held mechanical stirrer, thermometer, and gas inlet tube exbetween c and140 tending below the liquid surface was charged 13.2 lbs. of

Example Ill-Preparation of 2-amino-4,6-bis(dimethylamino)-s-triazine at atmospheric pressure 2,4-bis(dimethylamino)-6-chloro-s-triazine dissolved in 3 References Cited gal. of dimethylsulfoxide. The stirred solution was heate t at 135l40 C. and anhydrous ammonia gas was passed UNITED STATES PATENTS in through the gas inlet tube until gas absorption ceased. 2,222,350 9 Keller et a1 260249.6 The time elapsed when gas absorption ceased was 8-10 2,223,161 941 Zerweck et al 260249.6 hours. The reaction solution was then cooled and poured 2,909,421 10/ 1959 Gysln XR into 5 gal. of water and the precipitated crude product was 9 11/1964 xt r et al- 260249.6 XR collected by filtration. After air-drying the crude product OTHER REFERENCES collected from five such runs, they were combined and treated with 3 N aqueous hydrochloric acid (1.75 liters/ Borkovec et Medlclnal & Pharmt chemo 2.2 lbs. of solid). The resulting slurry was filtered and PP- 457-61 the filtrate was treated with 50% aqueous sodium hydoxide Pearlman et chem- PP- 3726-8 solution until basic. The solids precipitated by addition (1948)- of a ueous base were collected as Crop I.

A second crop of purified product was obtained by HENRY JILES Pnmary Exammer treating the original filtration residue with 3 N aqueous JOHN M, FORD, A i t t E i hydrochloric acid at 5055, cooling to 10 C. and filtering. The filtrate affords Crop II upon basifying with 50% US. Cl. X.R. aqueous sodium hydroxide and collecting by filtration. 65 260249.8 

